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PLK1‐dependent phosphorylation restrains EBNA2 activity and lymphomagenesis in EBV‐infected mice
Author(s) -
Zhang Xiang,
Schuhmachers Patrick,
Mourão André,
Giansanti Piero,
Murer Anita,
Thumann Sybille,
KuklikRoos Cornelia,
Beer Sophie,
Hauck Stefanie M,
Hammerschmidt Wolfgang,
Küppers Ralf,
Kuster Bernhard,
Raab Monika,
Strebhardt Klaus,
Sattler Michael,
Münz Christian,
Kempkes Bettina
Publication year - 2021
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.202153007
Subject(s) - german , library science , research center , art history , history , political science , computer science , law , archaeology
While Epstein–Barr virus (EBV) establishes a life‐long latent infection in apparently healthy human immunocompetent hosts, immunodeficient individuals are at particular risk to develop lymphoproliferative B‐cell malignancies caused by EBV. A key EBV protein is the transcription factor EBV nuclear antigen 2 (EBNA2), which initiates B‐cell proliferation. Here, we combine biochemical, cellular, and in vivo experiments demonstrating that the mitotic polo‐like kinase 1 (PLK1) binds to EBNA2, phosphorylates its transactivation domain, and thereby inhibits its biological activity. EBNA2 mutants that impair PLK1 binding or prevent EBNA2 phosphorylation are gain‐of‐function mutants. They exhibit enhanced transactivation capacities, accelerate the proliferation of infected B cells, and promote the development of monoclonal B‐cell lymphomas in infected mice. Thus, PLK1 coordinates the activity of EBNA2 to attenuate the risk of tumor incidences in favor of the establishment of latency in the infected but healthy host.